When a Newborn Has Mild Brain Stress at Birth, Does Cooling Help?

A plain-language look at the COMET pilot study of body cooling for babies with mild encephalopathy

Some babies have a difficult birth that briefly deprives the brain of oxygen, leaving them with mild signs of brain stress in the first hours of life. For babies with severe versions of this problem, doctors lower the baby's body temperature for three days — a treatment called cooling — and it clearly protects the brain. A recent pilot study called COMET tested whether that same cooling also helps babies with only mild signs, and found no brain-benefit and some short-term downsides, leaving this an open question that larger studies are now working to answer.

Why this question matters for families

When a baby is born and needs help breathing, doctors watch closely for signs that the brain was affected by a shortage of oxygen and blood flow around the time of birth — a condition called hypoxic-ischemic encephalopathy, or HIE. The signs range from severe to very mild. For babies at the more serious end, a treatment that gently lowers body temperature for about three days has been one of the biggest advances in newborn care, and it is now standard everywhere. But many babies show only mild signs — a little floppiness, jitteriness, or unusually strong reflexes — while otherwise looking well. Whether these mild babies should also be cooled is a genuine uncertainty, and it is the exact question the study described here set out to explore [1].

How cooling became common before anyone had tested it in mild cases

To see why this study was needed, it helps to know a little history. Cooling was proven to work through several large, carefully run trials in the 2000s: an international head-cooling study called CoolCap (Cool Cap for neonatal encephalopathy) [2], a U.S. National Institute of Child Health and Human Development (NICHD) body-cooling trial run at fifteen hospitals [3], and a UK-and-Europe trial called TOBY (Total Body Hypothermia for Neonatal Encephalopathy) [4]. Together these showed that cooling reduces death and serious disability, a conclusion confirmed when experts pooled the results [5]. The signs of brain stress were measured using a long-standing scoring system first described by two doctors named Sarnat in the 1970s [6]. But there was an important catch: every one of these trials only enrolled babies with moderate or severe signs. Babies with mild signs were left out, so no one actually knew whether cooling helped them.

For a long time, doctors assumed mild cases would simply recover on their own. Newer research changed that comfortable assumption. A study called PRIME (Prospective Research on Infants with Mild Encephalopathy) followed such babies and found that many had early warning signs [7], and when the same children were checked around 18 to 24 months, about one in six had a disability and a number had lower-than-average language and thinking scores [8]. Another review of many studies estimated that roughly a quarter of babies with mild HIE have some difficulty by 18 months [9]. Faced with that, and knowing cooling has to begin within six hours or not at all, many doctors started cooling mild babies "just in case" — even though experts who reviewed the limited evidence warned it was not enough to say cooling truly helps, or that it does no harm [10]. COMET was created to finally test the practice instead of guessing.

What the study did

COMET, which stands for Cooling in Mild Encephalopathy, was a pilot study — a first, smaller trial meant to see whether a bigger one is feasible and worthwhile [1]. It was carried out at six hospitals in the United Kingdom and Italy and included 101 newborns with carefully confirmed mild signs of brain stress and a normal reading on a simple brain-wave monitor. The babies were randomly assigned to one of three groups: normal temperature (kept warm and comfortable), cooling for 48 hours, or cooling for 72 hours. Because the decision is so time-sensitive, this random assignment is the fairest way to compare the choices without doctors' expectations tilting the result.

To measure the effect on the brain, the researchers used a special brain scan that detects a chemical called N-acetylaspartate (NAA), which is a marker of healthy brain tissue — higher levels generally mean a healthier brain. This marker was chosen because it is one of the best early predictors of how a baby will develop later [11]. The scans were done between four and seven days after birth.

What they found, and what it does and doesn't mean

The cooled babies did not have healthier brain-chemistry readings — in fact their NAA levels were somewhat lower, the opposite of what you would expect if cooling were protecting them [1]. Cooled babies were also about five times more likely to need a breathing tube, the 72-hour group stayed in the hospital nearly two days longer, and most cooled babies needed pain-and-comfort medicine and shivered during treatment. Serious complications were uncommon in all groups.

It would be a mistake, though, to conclude from this that cooling harms mild babies. There is a crucial catch the researchers are careful to point out: the babies who ended up in the cooling groups were sicker to begin with — they had needed more help at birth [1]. Because of how the study was organized, the more fragile babies were more likely to be cooled, so their lower brain readings and greater need for a breathing machine might simply reflect that they started off in worse shape, not that cooling caused it. A small pilot study cannot fully separate those two explanations. Reassuringly, the comfort medicines given during cooling have not been linked to worse development in other research [12], so that is not a reason for worry. The fair summary is that cooling showed no clear benefit for mild babies and came with real short-term burdens, in a study too small to give a final answer.

What cooling actually involves, if it is offered

It also helps to picture what the treatment itself is like, because that is part of the trade-off families weigh. During cooling, the baby lies on a special mattress that lowers body temperature to about 33.5 °C — a few degrees below normal — for two to three days, after which the baby is slowly rewarmed. Being cooler than normal can make a baby shiver and uncomfortable, so most cooled babies are given sedative and pain-relief medicine, which in turn can make them sleepier and less able to feed by mouth for a while. Cooling also usually means more monitoring lines, a longer stay in intensive care, and sometimes help from a breathing machine. None of this is dangerous in itself, and for babies with moderate or severe brain stress the protection cooling provides is well worth these inconveniences. The open question this study raises is whether the same trade-off makes sense for a baby whose brain stress is only mild, where the protective benefit has not been shown. That is why "watch carefully and keep the baby warm and comfortable" is a thoughtful choice for mild cases, not a lesser or lazy one — it spares the baby the burdens of a treatment that, for this group, has not yet proven it helps.

What this means for your baby, and what comes next

If your baby has mild signs of brain stress, the most important takeaways are these. Cooling remains a proven, valuable treatment for babies with moderate or severe signs [3] [4] — this study does not change that, and if your baby's signs are in that more serious range, cooling is the right and well-established choice. It is also worth knowing that mild signs are not always the final picture: in the first day of life a baby's neurological examination can change in either direction, which is one reason the care team repeats the gentle examination over the first hours and days. If the signs deepen into the moderate range, the plan can shift and the baby would then meet the established criteria for cooling. So a decision to watch rather than cool at the outset is not a door that closes — it is careful observation with the option to act if the situation changes. For mild signs, careful watching with repeated gentle examinations is a reasonable and common approach, partly because mild signs sometimes progress and the plan may change. If a team does recommend cooling for a mild case, it is fair to ask why, and to understand that this is an area where doctors are still genuinely uncertain rather than following settled proof [10]. Researchers around the world are now running larger trials to answer the question properly [1], and one of the most helpful things families can do, when offered, is to take part in such a study — that is how the next generation of babies will get a clear answer. In the meantime, a team that chooses watchful, warm, attentive care for a mildly affected baby is making a defensible, evidence-aware choice.

References

  1. Montaldo P, Cirillo M, Burgod C, et al. Whole-body hypothermia vs targeted normothermia for neonates with mild encephalopathy: a multicenter pilot randomized clinical trial. JAMA Netw Open. 2024;7(5):e249119. doi:10.1001/jamanetworkopen.2024.9119 ↩
  2. Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005;365(9460):663-670. doi:10.1016/S0140-6736(05)17946-X17946-X) ↩
  3. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574-1584. doi:10.1056/NEJMcps050929 ↩
  4. Azzopardi DV, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361(14):1349-1358. doi:10.1056/NEJMoa0900854 ↩
  5. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;(1):CD003311. doi:10.1002/14651858.CD003311.pub3 ↩
  6. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study. Arch Neurol. 1976;33(10):696-705. doi:10.1001/archneur.1976.00500100030012 ↩
  7. Prempunpong C, Chalak LF, Garfinkle J, et al. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018;38(1):80-85. doi:10.1038/jp.2017.164 ↩
  8. Chalak LF, Nguyen KA, Prempunpong C, et al. Prospective research in infants with mild encephalopathy identified in the first six hours of life: neurodevelopmental outcomes at 18-22 months. Pediatr Res. 2018;84(6):861-868. doi:10.1038/s41390-018-0174-x ↩
  9. Conway JM, Walsh BH, Boylan GB, Murray DM. Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome - a systematic review. Early Hum Dev. 2018;120:80-87. doi:10.1016/j.earlhumdev.2018.02.007 ↩
  10. Kariholu U, Montaldo P, Markati T, et al. Therapeutic hypothermia for mild neonatal encephalopathy: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2020;105(2):225-228. doi:10.1136/archdischild-2018-315711 ↩
  11. Lally PJ, Montaldo P, Oliveira V, et al. Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multicentre cohort study. Lancet Neurol. 2019;18(1):35-45. doi:10.1016/S1474-4422(18)30325-930325-9) ↩
  12. Gundersen JK, Chakkarapani E, Jary S, et al. Morphine and fentanyl exposure during therapeutic hypothermia does not impair neurodevelopment. EClinicalMedicine. 2021;36:100892. doi:10.1016/j.eclinm.2021.100892 ↩